Faghih Zahra, Rezaeifard Somayeh, Safaei Akbar, Ghaderi Abbas, Erfani Nasrollah
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, e-mail:
Iran J Immunol. 2013 Dec;10(4):193-204.
CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile.
To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer.
Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status.
The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively).
As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.
CD8 + 细胞毒性T淋巴细胞最近根据其细胞因子表达谱进行了分类。
评估乳腺癌患者肿瘤引流淋巴结（TDLN）中CD8 + 淋巴细胞及其效应子亚群（包括Tc1、Tc2和Tc17）的百分比。
从42例乳腺癌患者的TDLN中获得单细胞悬液。使用适当的荧光染料偶联抗体对细胞表面标志物和细胞内细胞因子进行染色。数据在四色流式细胞仪上采集，并通过CellQuestPro软件包进行分析。在CD8 + T淋巴细胞中定量不同CD8 + 细胞亚型（Tc1、Tc2和Tc17）的百分比。对LN + 与LN - 患者以及不同临床病理状态的患者进行比较。
LN + 和LN - 患者之间Tc1、Tc2和Tc17亚群的百分比无显著差异。尽管浸润性导管癌（IDC）的LN + 患者中Tc1细胞的百分比没有差异，但与LN - 患者相比，Tc1细胞产生的IFN - γ平均表达显著降低。另一方面，晚期患者中Tc2和Tc17效应子亚群的百分比增加（分别为p = 0.018和p = 0.009）。
作为第一项研究乳腺癌患者TDLN中CD8 + 淋巴细胞各种效应子亚型的研究，我们的数据共同表明，TDLN中产生IL - 17和IL - 4的CD8 + T细胞百分比（Tc2和Tc17）与乳腺癌进展呈正相关。尽管Tc1细胞的数量似乎不受癌症进展的影响，但这些细胞中IFN - γ的下调似乎与肿瘤转移至TDLN有关。这些发现可能对基于CD8 + 效应子亚群的癌症免疫治疗有影响。
